PMID- 31391260
OWN - NLM
STAT- MEDLINE
DCOM- 20200706
LR  - 20200706
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 39
IP  - 39
DP  - 2019 Sep 25
TI  - Change in Brain Plasmalogen Composition by Exposure to Prenatal Undernutrition 
      Leads to Behavioral Impairment of Rats.
PG  - 7689-7702
LID - 10.1523/JNEUROSCI.2721-18.2019 [doi]
AB  - Epidemiological studies suggest that poor nutrition during pregnancy influences 
      offspring predisposition to experience developmental and psychiatric disorders. 
      Animal studies have shown that maternal undernutrition leads to behavioral 
      impairment, which is linked to alterations in monoaminergic systems and 
      inflammation in the brain. In this study, we focused on the ethanolamine 
      plasmalogen of the brain as a possible contributor to behavioral disturbances 
      observed in offspring exposed to maternal undernutrition. Maternal food or 
      protein restriction between gestational day (GD) 5.5 and GD 10.5 resulted in 
      hyperactivity of rat male adult offspring. Genes related to the phospholipid 
      biosynthesis were found to be activated in the PFC, but not in the NAcc or 
      striatum, in the offspring exposed to prenatal undernutrition. Corresponding to 
      these gene activations, increased ethanolamine plasmalogen (18:0p-22:6) was 
      observed in the PFC using mass spectrometry imaging. A high number of crossings 
      and the long time spent in the center area were observed in the offspring exposed 
      to prenatal undernutrition and were mimicked in adult rats via the intravenous 
      injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the 
      liposome. Additionally, plasmalogen (18:0p-22:6) increased only in the PFC, and 
      not in the NAcc or striatum. These results suggest that brain plasmalogen is one 
      of the key molecules to control behavior, and its injection using liposome is a 
      potential therapeutic approach for cognitive impairment.SIGNIFICANCE STATEMENT 
      Maternal undernutrition correlates to developmental and psychiatric disorders. 
      Here, we found that maternal undernutrition in early pregnancy led to 
      hyperactivity in rat male offspring and induced gene activation of 
      phospholipid-synthesizing enzyme and elevation of ethanolamine plasmalogen 
      (18:0p-22:6) level in the PFC. Intravenous injection of ethanolamine plasmalogen 
      (18:0p-22:6) incorporated into the liposome maintained crossing activity and the 
      activity was circumscribed to the center area for a long time period, as in 
      prenatally undernourished offspring with aberrant behavior. Furthermore, the 
      amount of ethanolamine plasmalogen (18:0p-22:6) increased in the PFC of the rat 
      after injection. Our result suggests that brain plasmalogen is one of the key 
      molecules to control behavior and that its injection using liposome is a 
      potential therapeutic approach for cognitive impairment.
CI  - Copyright (c) 2019 the authors.
FAU - Hino, Kodai
AU  - Hino K
AD  - Division of Anatomy and Cell Biology, Department of Anatomy, Shiga University of 
      Medical Science, Otsu 520-2192, Japan.
FAU - Kaneko, Shunya
AU  - Kaneko S
AD  - Division of Anatomy and Cell Biology, Department of Anatomy, Shiga University of 
      Medical Science, Otsu 520-2192, Japan.
FAU - Harasawa, Toshiya
AU  - Harasawa T
AD  - Division of Anatomy and Cell Biology, Department of Anatomy, Shiga University of 
      Medical Science, Otsu 520-2192, Japan.
FAU - Kimura, Tomoko
AU  - Kimura T
AD  - Division of Anatomy and Cell Biology, Department of Anatomy, Shiga University of 
      Medical Science, Otsu 520-2192, Japan.
FAU - Takei, Shiro
AU  - Takei S
AD  - Department of Environmental Biology, College of Bioscience and Biotechnology, 
      Chubu University, Kasugai 487-8501, Japan.
FAU - Shinohara, Masakazu
AU  - Shinohara M
AD  - Division of Epidemiology, Kobe University Graduate School of Medicine, Kobe 
      650-0017, Japan.
AD  - Integrated Center for Mass Spectrometry, Kobe University Graduate School of 
      Medicine, Kobe 650-0017, Japan.
FAU - Yamazaki, Fumiyoshi
AU  - Yamazaki F
AD  - International Mass Imaging Center and Department of Cellular and Molecular 
      Anatomy, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
FAU - Morita, Shin-Ya
AU  - Morita SY
AUID- ORCID: 0000-0003-4079-707X
AD  - Department of Pharmacy, Shiga University of Medical Science Hospital, Shiga 
      520-2192, Japan.
FAU - Sato, Shumpei
AU  - Sato S
AD  - International Mass Imaging Center and Department of Cellular and Molecular 
      Anatomy, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
FAU - Kubo, Yoshihito
AU  - Kubo Y
AD  - Division of Anatomy and Cell Biology, Department of Anatomy, Shiga University of 
      Medical Science, Otsu 520-2192, Japan.
FAU - Kono, Tadaaki
AU  - Kono T
AD  - Division of Anatomy and Cell Biology, Department of Anatomy, Shiga University of 
      Medical Science, Otsu 520-2192, Japan.
FAU - Setou, Mitsutoshi
AU  - Setou M
AUID- ORCID: 0000-0002-1302-6467
AD  - International Mass Imaging Center and Department of Cellular and Molecular 
      Anatomy, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
AD  - Preeminent Medical Photonics Education & Research Center, Shizuoka 431-3192, 
      Japan.
AD  - Department of Anatomy, University of Hong Kong, Pokfulam, Hong Kong SAR, China.
FAU - Yoshioka, Mina
AU  - Yoshioka M
AD  - Division of Anatomy and Cell Biology, Department of Anatomy, Shiga University of 
      Medical Science, Otsu 520-2192, Japan.
FAU - Fujino, Junya
AU  - Fujino J
AUID- ORCID: 0000-0002-5285-2032
AD  - Division of Anatomy and Cell Biology, Department of Anatomy, Shiga University of 
      Medical Science, Otsu 520-2192, Japan.
FAU - Sugihara, Hiroyuki
AU  - Sugihara H
AD  - Division of Molecular Diagnostic Pathology, Department of Pathology, Shiga 
      University of Medical Science, Otsu 520-2192, Japan.
FAU - Kojima, Hideto
AU  - Kojima H
AD  - Department of Stem Cell Biology and Regenerative Medicine, Shiga University of 
      Medical Science, Otsu 520-2192, Japan, and.
FAU - Yamada, Naoto
AU  - Yamada N
AD  - Department of Psychiatry, Shiga University of Medical Science, Otsu 520-2192, 
      Japan.
FAU - Udagawa, Jun
AU  - Udagawa J
AUID- ORCID: 0000-0002-6573-9434
AD  - Division of Anatomy and Cell Biology, Department of Anatomy, Shiga University of 
      Medical Science, Otsu 520-2192, Japan, udagawa@belle.shiga-med.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190807
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Plasmalogens)
RN  - 0 (phosphatidal ethanolamines)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*physiology
MH  - Female
MH  - Male
MH  - Malnutrition/*complications/metabolism
MH  - Plasmalogens/*metabolism
MH  - Prefrontal Cortex/*metabolism
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*metabolism
MH  - Rats
MH  - Rats, Wistar
PMC - PMC6764206
OTO - NOTNLM
OT  - hyperactivity
OT  - maternal undernutrition
OT  - plasmalogen phosphatidylethanolamine
OT  - prefrontal cortex
EDAT- 2019/08/09 06:00
MHDA- 2020/07/07 06:00
PMCR- 2020/03/25
CRDT- 2019/08/09 06:00
PHST- 2018/10/21 00:00 [received]
PHST- 2019/07/28 00:00 [revised]
PHST- 2019/07/31 00:00 [accepted]
PHST- 2019/08/09 06:00 [pubmed]
PHST- 2020/07/07 06:00 [medline]
PHST- 2019/08/09 06:00 [entrez]
PHST- 2020/03/25 00:00 [pmc-release]
AID - JNEUROSCI.2721-18.2019 [pii]
AID - 2721-18 [pii]
AID - 10.1523/JNEUROSCI.2721-18.2019 [doi]
PST - ppublish
SO  - J Neurosci. 2019 Sep 25;39(39):7689-7702. doi: 10.1523/JNEUROSCI.2721-18.2019. 
      Epub 2019 Aug 7.